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FUNGAL PROPHYLAXIS BY ORAL ADMINISTRATION OF BOVINE ANTI-CANDIDA ANTIBODIES IN ALLOGENEIC BMT.

Allogeneic bone marrow transplant recipients (BMT) are at high risk of developing invasive fungal infections by Candida species. Invasive Candida infections are of endogenous origin, developing from gastrointestinal colonization. A majority of BMT patients are colonized before and during the transplant proceedure.
Material & Methods: We performed a pilot trial with bovine anti-Candida-antibodies derived from the colostrum of cows immunized against Candida mannan antigen. Nineteen patients were first followed to evalauate the colonization pattern by quantitative fungal cultures in specimens from the mouth, urine and feaces. Patients with more than 100 CFU/ml of Candida in saliva before BMT had a stable or increasing colonization rate during BMT and 11 patients of these rate were studied. One patient was later excluded due to systemic antifungal therapy for a suspected invasive fungal infection. Antibody treatment consisted of 10 g of bovine anti-Candida antibodies containing 4.2 g of IgG, divided into 3 daily doses from day 4 before transplantation up to day 28 after BMT. The product was administered orally as a swish and swallow formula dispersed in chocolate drink. All patients also received topical nystatin (0.8 x 106U/day). Patients were followed by quantitative mouth wash cultures twicw weekly during the study, stool as well as serum samples were collected and analysed for any remaining bovine protein.
Results: Evaluation of the colonization revealed that 48 % of BMT recipients were colonised with Candida pre-BMT and the rate increased to 72 % beeing colonized at some time during BMT. The majority of fungal isolates were Candida albicans. Compliance was a problem due to severe mucositis and the patients could take antibodies for a median of 6 out of 33 days ( range 2 - 28 days). Response was seen in 7 out of 10 patients that recieved antibodies, with a reduction of CFU:s during therapy and 1 patient became completely negative during therapy. No adverse events were noted, some undigested or partly digested bovine proteins could be found in stool samples and only minute amounts could be found in serum samples.
Conclusion: A pilot trial with topical bovine anti-Candida-antibodies as oral colonization prophylaxis revealed favourable results, reducing colonization rate in 7 /10 patients and a complete erradication in 1 patient. Thus encouring further larger studies to evaluate the prophylactic possibility in immunosuppressed patients.

J Tollemar, N Gross, P Törner, C Jarstrand, L Hammarström & O Ringdén. Div. of Transplantation Surgery, Clinical Immunology and Clinical Bacteriology, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden

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